Donor Modulation of Strong Near-Infrared Lipid-Droplet Probes for in Vivo Diagnosis of Nonalcoholic Fatty Liver Disease

Lipid droplet accumulation is a pathological hallmark of nonalcoholic fatty liver disease (NAFLD); however, the utility of current lipid droplet-targeted fluorescent probes for in vivo diagnosis is hindered by shallow tissue penetration and strong background autofluorescence. To overcome these challenges, here, we report three donor–acceptor–acceptor solvatochromic probes (CTBT-ANPy, PTBT-ANPy, and MOPTBT-ANPy) with tunable electron-donating groups, enabling near-infrared (NIR) imaging of lipid droplets and in vivo NAFLD diagnosis. Owing to multiple intramolecular interactions and restriction of twisted intramolecular charge transfer, these probes exhibit intense NIR emissions (up to 709 nm, quantum yield of 34.2%) in low-polarity media. These lipophilic probes display high lipid-droplet specificity with bright light-up signals and wash-free capacity. With the aid of NIR-emissive MOPTBT-ANPy, in vivo high-contrast fluorescent discrimination of NAFLD in a mouse model was successfully achieved. This study underscores the potential of high-performance NIR probes for noninvasive accurate NAFLD diagnosis and monitoring.